Eosinophilias are naturally occurring components in the mammalian blood which have activities like that of other white blood cells (lymphocytes). Eosinophilia means "an increase of such eosinophils circulating in the blood. The precise function of the eosinophils is not established, but they appear to be a first line of defense against parasitic invasions of the blood stream. They could also play a marked role in allergies and inflammation. Normally, a droplet of blood (e.g. a cubic millimeter) contains as many as 350 eosinophils. In patients with the ailment, EMS, there are 1,000-12,000 eosinophils per cubic millimeter.
In the fall of 1989, medical investigators at the Federal Center for Disease Control reported discovery of the reason for a recent outbreak of the rare disease, EMS, apparently, it was linked to at least one source of the nutritional supplement, L-tryptophan, which had become contaminated in the manufacturing process. L-tryptophan (L-TTP) (chemically, 1-alpha-aminoindole-3-propionic acid) is an essential amino acid, which is normally ingested as a constituent of dietary protein, but is not synthesized by the human body. It was first isolated from the milk protein, casein, early in this century. For many decades, L-tryptophan has been capable of laboratory synthesis by any of several routes, now well known in organic chemistry. Possibly, the once patented synthesis, starting with alpha-ketoglutaric acid phenylhydrazine, is the currently preferred mode of industrial-scale manufacture. Having a single asymmetric carbon atom, (alpha on the side chain), it is normally a mixture of two optically active antipodes.
L-tryptophan may be depicted by the planar structural formulas as follows:
HOOC--(NH.sub.2) CH--CH.sub.2 -- Indole, with unsubstituted indole have the molecular formula C.sub.8 H.sub.7 N, also called 2,3-Benzopyrole.
L-tryptophan has long been approved by the Federal F & DA as a dietary supplement, but the compound has not yet been the subject of an approved New Drug Application (NDA), despite its established and expanding pharmacology in the literature. L-tryptophan is an essential nutrient with an estimated adult intake of 600 to 1220 mg daily.
In the formulation of L-tryptophan into dietary compositions, which are suitable for unit dosage administration, other [than] biologically inert compounds, like fillers and lubricants, are routinely employed; but heretofore, none of them have been recognized as being implicated in the newly observed EMS pathology in patients with some formulations of L-TTP.
EMS appears to have a subacute onset with clinical symptoms developing over several weeks. Patients typically complain of myalgia and fatigue. The myalgia is intense and often incapacitating. Many patients have respiratory complaints--dyspnea and cough, are especially common. There may be frank muscle weakness, distinct from any loss of extremity function caused by the severe myalgia. In some, the symptoms of EMS are distressing and serious and invite aggressive medical management.
As of Jan. 9, 1990, the number of officially reported EMS cases had climbed to 1046, for which the CDC has collected 429 completed report forms. In the evaluation of these forms, 98% had a history of L-tryptophan ingestion preceding the onset of symptoms. The duration of L-tryptophan use spanned from days to years with doses ranging from 26 mg to 15,000 mg per day; median, 1500 mg per day. 87% of the patients reported the onset of symptoms during or after July 1989, while 32% required hospitalization. Of the initial 30 cases reported (Nov. 13, 1989), eosinophil counts ranged from 2064 to 12,100 cells per mm; mean, 2300 cells per mm (normal; 50-350 cells per mm). [Presented are twenty cases satisfying the criteria for EMS as detailed by the CDC.]